Fleaborne Typhus–Associated Deaths — Los Angeles County, California, 2022

Los Angeles County, California, 2022

Jemma Alarcón, MD; Armine Sanosyan, MPH; Zuelma A. Contreras, PhD; Van P. Ngo, MPH; Ann Carpenter, DVM; Jill K. Hacker, PhD; William S. Probert, PhD; Dawn Terashita, MD; Sharon Balter, MD; Umme-Aiman Halai, MD

Disclosures

Morbidity and Mortality Weekly Report. 2023;72(31):838-843.

Abstract and Introduction

Abstract

Fleaborne typhus (also known as murine typhus), a widely distributed vectorborne zoonosis caused by Rickettsia typhi, is a moderately severe, but infrequently fatal illness; among patients who receive doxycycline, the case-fatality rate is <1%. Fleaborne typhus is a mandated reportable condition in California. Reported fleaborne typhus cases in Los Angeles County have been increasing since 2010, with the highest number (171) reported during 2022. During June–October 2022, Los Angeles County Department of Public Health learned of three fleaborne typhus–associated deaths. This report describes the clinical presentation, illness course, and methods used to diagnose fleaborne typhus in these three cases. Severe fleaborne typhus manifestations among these cases included hemophagocytic lymphohistiocytosis, a rare immune hyperactivation syndrome that can occur in the infection setting; myocarditis; and septic shock with disseminated intravascular coagulation. Increased health care provider and public health awareness of the prevalence and severity of fleaborne typhus and of the importance of early doxycycline therapy is essential for prevention and treatment efforts.

Introduction

Fleaborne typhus is transmitted from infected fleas by inoculation of flea feces into the flea bite site, a skin abrasion, or mucous membranes.^[1] The Oriental rat flea (Xenopsylla cheopis), a parasite of rats, is the historical vector.^[2] The cat flea (Ctenocephalides felis), whose principal host is the domestic cat (but which is also found on opossums, dogs, and rats) is the predominant vector in suburban areas of the United States*.^[3] Signs and symptoms of fleaborne typhus include fever, headache, a palm- and sole-sparing rash, hepatitis, and thrombocytopenia.^[4] Approximately one third of infected patients require intensive care for associated aseptic meningitis, seizures, adult respiratory distress syndrome, or septic shock;^[4] however, among patients who receive doxycycline therapy, the case-fatality rate is <1%.^[5] Most current cases in the United States are identified in California, Hawaii, and Texas.^[4] During 1985–2015, among 3,048 fleaborne typhus cases in Texas, 11 (0.4%) were fatal.^[6] The disease is endemic in Los Angeles County (LAC), and reporting is mandated in California (Figure). Before 2022, the most recent fleaborne typhus–associated death in LAC was reported in 1993.

(Enlarge Image)

Figure.

Fleaborne typhus cases, by year — Los Angeles County, California* 2010–2022
*Excluding the cities of Pasadena and Long Beach; data include confirmed, probable, and suspected cases.

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Abstract and Introduction
Methods
Results
Discussion
References
Sidebar

*http://www.publichealth.lacounty.gov/acd/vectortyphus.htm (Accessed January 25, 2023).

Table. Demographic, epidemiologic, and clinical characteristics of persons who died from fleaborne (murine) typhus–related illness — Los Angeles County, California, June–October 2022
Characteristic	Patient
Characteristic	A	B	C
Age, yrs (sex)	68 (male)	49 (female)	71 (male)
Ethnicity*	Hispanic	Hispanic	Hispanic
Signs and symptoms	Fever for 3 days and progressive lower extremity weakness	Headache, fever, chills, night sweats, and back pain for 7 days	Fever, disorientation, hypotension, AF with rapid ventricular response, and petechial rash (on legs and torso)
Potential exposure	Proximity of the patient's home to a highway and litter	Stray kittens in patient's backyard	Lived in an encampment inhabited by persons experiencing homelessness
Underlying medical conditions	Diffuse lymphadenopathy, obesity, hypertension, DM type 2, PVD, and chronic left foot ulcer	Obesity, hypertension, hyperlipidemia, and DM type 2	Alcohol and methamphetamine use
Abnormal laboratory values (referent range)
White blood cell count (4.5–10.0/μl)	—^†	—^†	3.4
Immature neutrophils (<10%)	—^†	—^†	15
Platelet count (160–360/μl)	—^†	130	31
Hemoglobin (13.5–16.5/μl)	10.4	—^†	10.1
Sodium (135–145 mmol/L)	126	—^†	—^†
Potassium (3.5–5.1 mmol/L)	—^†	2.8	—^†
Magnesium (1.6–2.6 per md/dL)	—^†	1.5	—^†
Total bilirubin (<1 mg/dL)	—^†	—^†	1
Alanine aminotransferase (10–50 U/L)	143	114	73
Aspartate aminotransferase (10–50 U/L)	102	141	224
Venous lactate (0.5–1.6 mmol/L)	2.6	—^†	4.8
C-reactive protein (<0.3 mg/L)	—^†	269.2	—^†
Treatments received	Cefepime, vancomycin, piperacillin-tazobactam, etoposide, dexamethasone, fluconazole, and trimethoprim-sulfamethoxazole	Ceftriaxone, vancomycin, and meropenem	Ceftriaxone, vancomycin, acyclovir, and penicillin
Doxycycline therapy started, hospital day	18	2	2
Major clinical events	Mental status deterioration, hypotension, AF with rapid ventricular response, hypoxic respiratory failure, HLH, and severe septic shock	SVT, two episodes of cardiac arrest, and multiorgan failure	Hypoxemic respiratory failure, multiorgan failure, and DIC
Microbiology results	Epstein-Barr virus infection diagnosed by PCR (hospital days 9 and 16), HSV 1 diagnosed by bronchoscopy specimen, (hospital day 16), multidrug resistant Escherichia coli detected in blood cultures, and CMV diagnosed by PCR (hospital day 29)	Parvovirus B19 DNA was detected in blood and heart tissue by PCR	—^†
Rickettsia typhi molecular testing results
Titer collection timing, hospital day	19	2	2
Titer result timing, hospital day	28	Patient deceased	Patient deceased
Titer result
IgM titer	>1:256	1:128	1:128
IgG titer	>1:256	1:64	>1:256
VRDL result
IgG titer	Not submitted	>1:1,024	Not submitted
PCR result	Not submitted	Positive	Positive
Karius test^§
Timing, hospital day	18	Not submitted	Not submitted
Result	Positive for R. typhi	—^†	—^†
Days to death after hospitalization	30	3	5
Cause of death^¶	Fleaborne typhus–induced HLH and septic shock	Myocarditis	Septic shock associated with shock liver, hyperkalemia, and lactic acidosis

Abbreviations: AF = atrial fibrillation; CMV = cytomegalovirus; DIC = disseminated intravascular coagulation; DM = diabetes mellitus; HLH = hemophagocytic lymphohistiocytosis; HSV = herpes simplex virus; Ig = immunoglobulin; PCR = real-time polymerase chain reaction; PVD = peripheral vascular disease; SVT = supraventricular tachycardia; VRDL = Viral and Rickettsial Disease Laboratory.
*Persons of Hispanic or Latino (Hispanic) origin might be of any race but are categorized as Hispanic.
^†Result within normal limits.
^§A noninvasive, rapid cell-free DNA-based diagnostic test capable of identifying bacteria, mycobacteria, DNA viruses, fungi, and protozoa in blood. Host and microbial cell-free DNA isolated from the patient's blood specimen is sequenced then analyzed using bioinformatics of DNA-based pathogen genomes. The test is useful for identifying rare pathogens. https://kariusdx.com/
^¶As recorded on the death certificate.